This instrumentation grant proposal requests funds for a Leica LMD 7000 laser microdissection microscope/system, a critical tool for ongoing NIH-supported biomedical research projects at the University of Iowa (UI). The proposed microscope will provide high-end capabilities for seeking out and collecting very specific, targeted cell and tissue samples for follow-up studies on the molecular genetics and immunologic underpinnings of human diseases of great relevance for public health. The UI currently has one laser microdissection microscope to serve the entire campus; however, the instrument is obsolete, difficult to use, expensive to repair, and has recently experienced tons of downtime. Clearly, it needs to be replaced with a modern instrument that will be adequate for the research of the 11 UI investigators that take part in this application Five of 11 investigators will use the LMD 7000 for cancer research: Siegfried Janz seeks to understand the genetic pathways of plasma cell tumor formation; Andean Burnett attempts to develop targeted therapies for patients with head and neck cancer; Hasem Habelhah elucidates mechanisms of cFLIP expression and RIP1 cleavage in tumor cells; George Weiner evaluates therapeutic antibodies for use in novel lymphoma treatment and prevention approaches; and Dawn Quelle assesses the potential utility of PARF as a prognostic biomarker for pancreatic and brain cancer. 6 of 11 investigators will take advantage of LMD 7000-assisted laser microdissection for research unrelated to cancer: Josef Comeron determines genetic recombination rates along individual chromosomes; Jeffery Murray and Martine Dunnwald perform genetic studies on cleft lip and palate formation; David Stolz and Aliye Uc examine organ damage in a newly developed pig model of human cystic fibrosis; Maureen Donovan studies transporter proteins in the nasal mucosa for improved drug delivery systems to the brain; and David Soll evaluates factors of pathogenicity in the yeast, Candida albicans, the frequent underlying reason of opportunistic infections in immunosuppressed patients. All studies described above - currently supported by $16,853,566 of active NIH research funding - would greatly benefit from the acquisition of a Leica LMD 7000. If this application will be awarded, the system will be set up in the UI Central Microscopy Research Facility. Dedicated facility personnel will administer and maintain the instrument, provide high-level technical assistance and training, and make it available 24/7 in order to accommodate as many users as possible. This application enjoys strong institutional commitment, as demonstrated by attached letters of support from the UI VP for Research, Dr. Cohen, and the Dean of the College of Medicine, Dr. Rothman.